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. 2022 Aug 10:13:930979.
doi: 10.3389/fimmu.2022.930979. eCollection 2022.

Mast cells and tryptase are linked to itch and disease severity in mycosis fungoides: Results of a pilot study

Dorothea Terhorst-Molawi  1   2   3 , Katharina Lohse  1   2 , Katharina Ginter  1   2 , Viktoria Puhl  1   2 , Martin Metz  1   2 , Man Hu  1   2 , Marcus Maurer  1   2 , Sabine Altrichter  1   2   4
Affiliations

Mast cells and tryptase are linked to itch and disease severity in mycosis fungoides: Results of a pilot study

Dorothea Terhorst-Molawi et al. Front Immunol. .

Abstract

Introduction: In mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, itch is a frequent clinical symptom. Whether mast cells (MCs), eosinophils (Eos) or their mediators play a role in MF-associated itch or disease severity is controversially discussed. Here, we explored the role of MC and Eo numbers in the skin as well as blood levels of their mediators in disease severity and itch.

Methods: In 10 patients with MF and 10 matched control subjects we assessed disease severity, itch, and quality of life impairment using dedicated tools such as the mSWAT, ItchyQoL and DLQI. We analyzed skin biopsies and measured serum levels of tryptase, a mast cell mediator, as well as of the eosinophil products eosinophil cationic protein (ECP) and major basic protein (MBP).

Results: The presence of chronic itch, in four of 10 patients, was associated with significantly higher disease severity (mSwat), larger body surface area affected, and stronger QoL impairment (Itchy-Qol, DLQI). Serum levels of tryptase, but not ECP and MBP, were linked with patient-reported disease severity, body surface area affected, and the presence of itch. Three of the four patients with chronic itch, but none of the six patients without, had tryptase levels above >6µg/l. Numbers of MCs in the papillary dermis were higher in MF skin lesions then in non-lesional skin of MF patients and skin of healthy controls.

Discussion: The MC-mediator tryptase, in MF, is linked to disease activity and impact, most prominently to itch. Our findings call for larger studies that explore the role of MCs, tryptase and other MC mediators as drivers of itch and their role in MF pathogenesis.

Keywords: cutaneous T-cell lymphoma; eosinophil; itch (pruritus); mast cell; mycosis fungoides; tryptase.

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Conflict of interest statement

DT-M has received research funds and was advisor for Celldex, Novartis, Sanofi and Moxie. MMe is or recently was a speaker and/or advisor for AbbVie, Amgen, ArgenX, AstraZeneca, Bayer, Celldex, Celgene, Escient, Galderma, Grünenthal, GSK, Menlo, Novartis, Pfizer, Pharvaris, Roche, Sanofi-Aventis, Third Harmonic Bio. MMa is or recently was a speaker and/or advisor for and/or has received research funding from Allakos, Aralez, Genentech, GSK, Menarini, Merckle Recordati, Moxie, Novartis, Sanofi, MSD, and Uriach. SA has conducted studies for received research funds/was advisor for Allakos, ALK, AstraZeneca, CSL Behring, LeoPharma, Moxie, Novartis, Sanofi, Takeda, Thermofisher. Published results are part of the study ROBERTIS, funded by AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mast cell counts in the papillary dermis of healthy patients and patients with MF. MF, Mycosis fungoides.
Figure 2
Figure 2
Blood tryptase counts correlate with disease severity and affected body surface area. (A) Serum Tryptase levels plottet against severity evaluated by patients using VAS (including depiction of linear correlation). (B) Tryptase versus disease severity evaluated by patients using rating scale (values given as mean and SD). (C) Tryptase versus disease severity evaluated by physicians using rating scale (values given as mean and SD). (D) Serum Tryptase levels plotted against affected body surface area (including depiction of linear correlation).
Figure 3
Figure 3
Differences of blood tryptase, MBP and ECP levels in MF patients with itch (itch) and without itch (no itch).
See this image and copyright information in PMC

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